The CHEK-2 gene

Besides the BRCA-genes, mutations occur in other genes that protect the individual from cancer development. Usually, these mutations have lower penetrance, which means that there is a lesser chance of developing cancer from these mutations. One of the most studied mutations besides BRCA-1 and BRCA-2 is the CHEK2-gene variant. CHEK2  is a gene located on chromosome 22, that encodes for a protein helping us to repair damaged DNA. A mutation in the CHEK2-gene inherited from one of the parents increases the breast cancer risk 2-fold. However, if the mutation exists in both the paternal and maternal inherited genes, the risk increases 6-fold. The gene mutation seems to be more frequent in the northern European populations, with 3% of people carrying the mutation  (Finish, Dutch), than in southern European populations (0.5%).  Although more rare than the BRCA-mutations, and incorporating a lesser risk for breast cancer, CHEK2 is currently considered the third most important breast cancer susceptibility gene. 

 

References:

1) Apostolou P1, Fostira F. Hereditary breast cancer: the era of new susceptibility genes.. Biomed Res Int. 2013;747318. doi: 10.1155/2013/

2) D. Easton. CHEK2 ∗1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies,” The American Journal of Human Genetics, 2004;74:1175–1182.

3) Liu C1, Wang Y, Wang QS, Wang YJ. The CHEK2 I157T variant and breast cancer susceptibility: a systematic review and meta-analysis.. Asian Pac J Cancer Prev. 2012;13:1355-60

4) S. Narod et al. Estimating survival rates after ovarian cancer among women tested for BRCA1 and BRCA2 mutations. Clinical Genetics 2012; 83:3:232–237

5) M. Gage, D. Wattendorf, and L. R. Henry. Translational advances regarding hereditary breast cancer syndromes. Journal of Surgical Oncology. 2012;105:5. 444–451

6) C. Cybulski, B. Gorski, T. Huzarski et al. Effect of CHEK2 missense variant 1157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations,” Journal ofMedical Genetics 2009; 46:132–135.